For the last 30 years, there has been a growing recognition that adult plasticity is a fundamental mechanism underlying a host of brain processes ranging from recovery after injury to learning and memory and involves multiple levels of the brain including synapses, neurons, neuronal circuits, representational maps, and even supporting metabolic and vascular systems. Enhancement of neuronal plasticity as a means of treatment of neurological disorders and injuries has not been fully utilized, although such treatments are an attractive alternative to more conventional treatments because they have few, if any, side effects. Could plasticity be exploited for protection from brain injury? We propose the hypothesis that one type of plasticity, neurovascular plasticity, could be exploited to completely protect the cortex from ischemic injury. The proposed multifaceted study is designed for detailed quantification to further answer specific hypotheses related to protection by neurovascular plasticity and its underlying mechanisms at the functional, metabolic, histological, vascular, and behavioral levels in both adult and old rats. PUBLIC HEALTH RELEVANCE: The brain, and especially the cortex, is plastic (i.e., mutable) as demonstrated for many brain processes ranging from recovery from injury to learning and memory. Could plasticity be further exploited to protect it from brain injury? Based on new findings from our laboratory, we propose the hypothesis that one type of plasticity, neurovascular plasticity, could indeed be exploited to completely protect the ischemic injury (stroke) in adult and old rats.